Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma

J Neurooncol. 2007 May;82(3):229-37. doi: 10.1007/s11060-006-9275-1. Epub 2006 Dec 7.

Abstract

Background: P53 and ATM are central checkpoint genes involved in the repair of DNA damage after ionising irradiation, which has been associated with risk of brain tumours. Therefore, we tested the hypothesis that polymorphisms and haplotypes in p53 and ATM could be associated with glioma and meningioma risk.

Material and methods: Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program.

Results: The global statistical test of glioblastoma and p53 haplotypes was p = 0.02. The haplotype analysis on glioblastoma revealed the 1-2-2 haplotype (promotor-codon72-intron 6) had a frequency of 6.1% in cases compared with 9.8% in controls (p = 0.003). The 1-2-1 haplotype was significantly more frequent in GBM cases, 10.2%, than in controls, 7.3% (p = 0.02). The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype in meningioma cases (33.8%) compared with controls (30.3%) (p = 0.03). The 2-1-2-1-1 haplotype had a lower frequency in meningioma cases (36.1%) than controls (40.7%) (p = 0.009).

Conclusions: This study found both positive and negative associations of haplotypes in p53 for glioblastoma and ATM for meningioma. This study provides new data that could add to our understanding of brain tumour susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ataxia Telangiectasia Mutated Proteins
  • Brain Neoplasms / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Glioma / genetics*
  • Haplotypes
  • Humans
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningioma / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk Factors
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases